The mechanism of proliferation of early intrathymic precursor cells is unknown.We analyzed this problem by two approaches. A: the possible involvement of several cytokines were investigated. B: monoclonal antibodies were generated that react with T-cell precursors and influence their proliferation. Both IL-1 and IL-2 are able to induce differentiation and growth of gamma/delta cells from CD4-/CD8- (DN) precursor cells. IL-2 induces the transcription of the TcR gamma chain gene when added to IL-1 plus mitogen cultured T-cell precursors. However, this does not result in an increase of surface TcR gamma/delta/CD3 complex expression. The results suggest that IL-2 may be involved in a critical step of development of gamma/delta T-cells, the induction of the TcR gamma chain gene. The 1.3.1 monoclonal antibody reacts with T-cells and several other cells and tissues. Biochemical analysis of the antigen and its tissue distribution suggest that the antibody recognizes a neutral amino peptidase on the cell surface. When added to DN cell cultures in the presence of IL-2 and PMA 1.3.1 stimulates thymidine incorporation (60%). We plan to purify the 1.3.1 antigen, to measure its peptidase activity and to determine its N-terminal amino acid sequence to answer the questions whether the antibody recognizes an aminopeptidase and whether the antigen identified is a novel protein with unknown structure.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000482-01
Application #
3808686
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code